Intratympanic Administration Of Dexamethasone Research Articles

Intratympanic administration of dexamethasone attenuates radiation induced damage to middle ear mucosa

Radiotherapy (RTx) is a highly effective treatment for head and neck cancer that can cause concurrent damage to surrounding healthy tissues. In cases of nasopharyngeal carcinoma (NPC), the auditory apparatus is inevitably exposed to radiation fields and sustains considerable damage, resulting in dysfunction. To date, little research has been conducted on the changes induced by RTx in the middle ear and the underlying mechanisms involved. Dexamethasone (DEX) is widely used in clinical practice because of its immunosuppressive and anti-inflammatory properties. The present study investigated the effects and underlying mechanisms of DEX delivered via intratympanic administration on RTx-induced damage to the middle ear and human middle ear epithelial (HMEE) cells. Sprague–Dawley (SD) rats were exposed to fractionated RTx (6.6 Gy/day for 5 days), and middle ear samples were collected at 1 and 4 months. Rats that received RTx presented a significant increase in the thickness of the submucosal layer in the middle ear and disorganization of the ciliated epithelium in the Eustachian tube (ET) mucosa. Importantly, intratympanic administration of DEX 30 min before RTx resulted in a lower degree of damage than that in the control group. Furthermore, DEX pretreatment downregulated the expression of cell death pathway markers in HMEE cells. Our collective results potentially support the use of DEX to reduce radiation-induced damage in the middle ear and may contribute to the development of future studies.

Tactics of treatment the children with pharyngeal tonsil hypertrophy in combination with otitis media with effusion

Actual tactics of treatment for children with otitis media with effusion in combination with pharyngeal tonsil hypertrophy involve medical treatment and observation for 3 months. The next step is to resolve the issue of surgical treatment, however, there are differences in its scope: adenotomy, tympanopuncture/myringotomy, ventilation tubes introduce may be performed. The modern method of adenotomy (endoscopic power assisted adenotomy) has advantages over the classical one due to precision and better possibilities of removal of lymphoid tissue in the peritubar and perichoanal parts of the nasopharynx. The aim of our study was to increase the effectiveness of surgical treatment of children with otitis media with effusion and pharyngeal tonsil hypertrophy. Prospective results of treatment for 47 children with otitis media with effusion in combination with pharyngeal tonsil hypertrophy were studied. In 47 children with otitis media with effusion in combination with pharyngeal tonsil hypertrophy, endoscopic energy adenotomy with tympanopuncture with intratympanic administration of dexamethasone was performed. At the time of adenotomy, all children had been suffering from otitis media with effusion for 3 months or more, and medical treatment had no effect. The examination 1 month after the intervention established, the secretion in the tympanic cavity in 6.4% of children who subsequently require insertion of ventilation tube. In 80.8% of cases, normalization of intratympanic pressure was observed in one month after adenotomy with tympanopuncture. The average values of intratympanic pressure in patients in 2 and 4 weeks after the simultaneously intervention was (76.5±7.8) dPa and (51.3±8.5) dPa, respectively. Power assisted adenotomy with simultaneous tympanopuncture is an effective method of treating children with otitis media with effusion and pharyngeal tonsil hypertrophy and can be recommended for use in clinical practice. Keywords: otitis, otitis with effusion, tonsils hypertrophy, tonsil pharyngeal, adenotomy, inflammatory diseases of the upper respiratory ways.

MEFV, IRF8, ADA, PEPD, and NBAS gene variants and elevated serum cytokines in a patient with unilateral sporadic Meniere's disease and vascular congestion over the endolymphatic sac

The etiology and underlying mechanism of Meniere's disease (MD) development are still unknown, although inflammation and autoimmunity have been implicated as underlying mechanisms. The human endolymphatic sac (ES) has been reported to have innate and adaptive immune capacity in local immune reactions. In vivo demonstration of inflammation of the ES in patients with MD is missing in the literature. We report the case of a 47-year-old female patient diagnosed with unilateral MD with genetic variants and cytokine markers indicating inflammation and vascular congestion of the ES. Endolymphatic hydrops in the right cochlea (grade 2) and vestibulum (grade 3) were detected using MRI. She carried heterozygous variants in MEFV (c.442G > C), IRF8 (c.1157G > T), ADA (c.445C > T), PEPD (c.151G > A), NBAS (c.4049T > C), CSF2RB (c.2222C > T), HPS6 (c.277G > T), IL2RB (c.1109C > T), IL12RB1 (c.1384G > T), IL17RC (c.260_271del GCAAGAGC TGGG), LIG1 (c.746G > A), RAG1 (c.650C > A), and SLX4 (c.1258G > C, c.5072A > G). In the serum, the levels of granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein 1α, and IL7 were significantly elevated, and the level of IL2Rα was reduced. Intratympanic administration of dexamethasone temporarily alleviated her hearing loss. Her vertigo was significantly relieved but remained slight after ES administration of corticosteroids.

Influence of Metabolic Syndrome on the Recovery from Idiopathic Sudden Sensorineural Hearing Loss.

Introduction Idiopathic sudden sensorineural hearing loss (ISSHL) is a disabling otologic urgency whose ethiopathogenesis is still controversial. Only in recent years metabolic syndrome (MetS) has been implicated as a possible aggravating factor in the prognosis of recovery from ISSHL. Objective To assess whether the preexistence of MetS interferes on hearing recovery levels. Methods Retrospective cohort study composed of adult (> 18 years old) ISSHL patients admitted for treatment between January 2015 and December 2019. To diagnose ISSHL, we used pure-tone audiometry, and identified MetS patients based on the criteria of the United States National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). The treatment protocol comprised hospitalization for five days for the intravenous administration of dexamethasone, audiometric surveillance, imaging and blood analyses, and, based on recovery, the planning of rescue treatments (intratympanic administration of dexamethasone and/or hyperbaric oxygen). The Siegel criteria were used to evaluate the hearing outcomes. Results The final sample was composed of 81 patients, 48 without MetS (nMetS) and 33 with MetS. Regarding the Siegel recovery category, the nMetS group had significantly better results ( p = 0.001), with 44% of complete recoveries against 6% in the MetS, and 58% of the MetS patients had the worst outcome, contrasting with 27% in the nMetS group. The nMetS group had an overall better evolution in terms of hearing recovery and had a significant improvement in the median hearing gain (20.6 dB versus 8.8 dB; p = 0.008). Additionally, the multivariate analysis revealed that the presence of MetS is a significant risk factor for a worse outcome (odds ratio [OR] = 0.30; 95% confidence interval [95%CI] = 0.10–0.85). Conclusion Regardless of age, gender, the initial audiometry threshold, and autoimmunity, MetS is a clear risk factor for a worse outcome regarding the recovery of hearing after ISSHL.

Intratympanic Steroid for the Management of Sudden Hearing Loss: Introduction of a Tapering Method.

Introduction:Sudden sensorineural hearing loss (SSNHL) is a therapeutic challenge. There are several controversies regarding the management protocol of SSNHL. This study aimed to present the results of a novel treatment algorithm, which is a combination of systemic steroids and a tapering intratympanic (IT) dexamethasone regimen. Materials and Methods:The past 10 years’ medical records of idiopathic SSNHL cases in Ghaem and Emamreza hospital, Mashhad University of Medical Sciences were evaluated. Patients were assessed using standardized methods for pure-tone threshold audiometry. The management method of SSNHL treatment included oral steroids combined with IT administration of dexamethasone once a day for 7 days and continuing it on an alternate day and then weekly basis. Patients’ recovery was assessed using Siegel’s criteria.Results:This study included a total of 248 cases of idiopathic sudden hearing loss, with a mean age of 40.63±16.19 years. In total, 105 (42.3%) and 143 (57.7%) patients were female and male, respectively. The most common associated symptoms included tinnitus (86.9%, n=205) followed by vertigo (52.1%, n=122). The final hearing outcome of patients showed that 39 (15.7%), 38(15.3%), 86 (34.7%), and 85 (34.3%) patients underwent a complete recovery, partial recovery, slight recovery, and no recovery, based on Siegel’s criteria. Conclusions:The dose, interval, and duration of IT steroid treatment were not universally approved. The treatment method designed based on a tapering of IT steroid injection in combination with already known systemic administration of steroids can be a treatment option in SSNHL patients.

Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma.

The treatment of acute hearing loss is clinically challenging due to the low efficacy of drug delivery into the inner ear. Local intratympanic administration of dexamethasone (D) and insulin-like growth factor 1 (IGF1) has been proposed for treatment, but they do not persist in the middle ear because they are typically delivered in fluid form. We developed a dual-vehicle drug delivery system consisting of cross-linked hyaluronic acid and polylactide-co-glycolide microcapsules. The effect and biocompatibility of the dual vehicle in delivering D and IGF1 were evaluated using an animal model of acute acoustic trauma. The dual vehicle persisted 10.9 times longer (8.7 days) in the middle ear compared with the control (standard-of-care vehicle, 0.8 days). The dual vehicle was able to sustain drug release over up to 1 to 2 months when indocyanine green was loaded as the drug. One-third of the animals experienced an inflammatory adverse reaction. However, it was transient with no sequelae, which was validated by micro CT findings, endoscopic examination, and histological assessment. Hearing restoration after acoustic trauma was satisfactory in both groups, which was further supported by comparable numbers of viable hair cells. Overall, the use of a dual vehicle for intratympanic D and IGF1 delivery may maximize the effect of drug delivery to the target organ because the residence time of the vehicle is prolonged.

Comparison of the protective efficacy between intratympanic dexamethasone and resveratrol treatments against cisplatin-induced ototoxicity: an experimental study

The main aim of this study was to compare the efficacy of intratympanic administration of dexamethasone and resveratrol in preventing cisplatin ototoxicity by measuring acoustic brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Forty rats (80 ears) were divided into five groups. Cisplatin was administered intraperitoneally to the first group (n = 8). Group 2 (n = 8) received cisplatin after resveratrol had been administered intratympanically. Group 3 (n = 8) received cisplatin after dexamethasone had been administered intratympanically. Group 4 (n = 8) received cisplatin after sodium chloride (NaCl) had been given intratympanically. Group 5 (n = 8) received cisplatin after dimethylsulfoxide (DMSO) had been given intratympanically. ABR and DPOAE tests were performed on all groups before and 72h after the procedure. ABR threshold values in rats that received dexamethasone and resveratrol were found to be less affected than those observed in the other post-cisplatin groups. ABR-IV and ABR-I-IV interval values were significantly reduced in rats that had been given dexamethasone and resveratrol compared to the other groups. After cisplatin treatment, otoacoustic emission (OAE) amplitudes were significantly decreased in Groups 1, 4, and 5 for all frequencies, while OAE values were sustained in the resveratrol and dexamethasone groups (Groups 2 and 3). At OAE frequency 5652, dexamethasone was more significantly associated with protective than resveratrol was, while no significant difference was found between the two groups at other OAE frequencies. In conclusion, intratympanic dexamethasone and intratympanic resveratrol treatments may provide a significant protection against cisplatin-induced ototoxicity.

The Effects of Experimental Intratympanic Steroid Administration on Organ of Corti Type 1 Spiral Ganglion.

Introduction It is unclear how effective is the intratympanic (IT) steroid treatment on organ of Corti type 1 spiral ganglion, its optimal dosage and frequency of administration. The effect of dexamethasone on cochlear functions in individuals with a normal hearing ability is also unknown. Objective The aim of this study was to evaluate, at the electrophysiological and ultrastructural levels, the effect of IT dexamethasone administration in guinea pigs with normal hearing on organ of Corti type 1 spiral ganglion. Methods A total of 20 guinea pigs ( n = 40 ears) whose hearing was detected to be normal by electrophysiological tests were included in the study and randomly divided into 6 groups. Four groups were considered study groups, while 2 groups were considered control groups. Dexamethasone was administered intratympanically in doses of 2 mg/mL and 4 mg/mL in the guinea pigs in the study groups. The animals in the control groups received physiological saline in equal doses as the study groups. All interventions were performed under general anesthesia, and the electrophysiological tests were repeated following the IT injections. Results No statistically significant differences were found among the groups when the IT injections were evaluated in terms of the electrophysiological measurements ( p > 0.05). The ultrastructural evaluation showed a cellular mitochondrial increase in the spiral ganglions of the cochlea in the groups in which dexamethasone was administered in a dose of 4 mg/mL. Conclusion According to the findings of this study, it can be suggested that the IT injection of dexamethasone is safe, and when applied in a dose of 4 mg/mL, it increases metabolic activity at the cellular level.

Evaluation of Adjuvant Intratympanic Dexamethasone Administration in the Treatment of Sudden Sensorineural Hearing Loss

MATERIALS and METHODS: Seventy-nine patients (41 F, 38 M) with a mean age of 48.2 years were included in the study. The data were collected by retrospective analysis of the patient records. The hearing levels of 36 patients treated with only SS (group I) and 43 patients treated with SS and ITS concomitantly (group II) were evaluated with pure tone audiometry tests at 500, 1000, 2000, 4000, and 8000 Hz frequencies in the pretreatment period and 1 and 3 months after treatment. RESULTS: The mean values of hearing thresholds in the audiometry performed in the pretreatment period and 1 and 3 months after treatment in the SS treatment group were 52.2±20, 39.5±25.3, and 35.3±25.3, respectively, while in the IT+SS treatment group, these values were determined as 60.7±19.9, 38.3±23.8, and 33.2±22.7, respectively. The improvements in mean hearing thresholds by time were statistically significantly different between the 2 groups (p<0.05).

突発性難聴に対する短期間連続デキサメサゾン鼓室内注入療法の単独初期治療としての効果

突発性難聴に対する短期間連続デキサメサゾン鼓室内注入療法の単独初期治療としての効果

Autoimmune inner ear disease associated with ankylosing spondylitis

We report here a case study of a 24-year-old man suffering from autoimmune inner ear disease who also suffered from ankylosing spondylitis (AS). Although he was previously diagnosed with AS, he has now presented with sensorineural hearing loss and vertigo. It is the first case that a patient with AS displays symptoms of autoimmune inner ear disease. His symptoms responded well to prednisolone treatment. However, because weight gain is a common side effect of steroid treatment and may exacerbate the lower back pain, which is symptomatic of AS, he has so far been treated with a minimum dosage of prednisolone. In addition, intratympanic administration of dexamethasone was effective to suppress the exacerbation of deafness.

Effect of intratympanic dexamethasone administration on cisplatin-induced ototoxicity in adult guinea pigs

To evaluate the effect and safety of intratympanic dexamethasone administration on cisplatin-induced ototoxicity in adult male guinea pigs and to assess the differences between early and late protection from this ototoxicity. Forty eight adult male guinea pigs were divided as follows: group I served as control group. Group II was subjected to intratympanic saline (subgroup IIa) or dexamethasone (subgroup IIb) injection. Group III was intraperitoneally injected with cisplatin. Groups IV and V were subjected first to intratympanic dexamethasone administration in both ears for 5 days starting 1 day and 1h - respectively - before cisplatin intraperitoneal injection. Dexamethasone intratympanic injection revealed similar functional and structural results compared with control. Cisplatin intraperitoneal injection resulted in a profound cochlear functional and structural damage in group III. Non-significant otoprotection resulted from intratympanic dexamethasone administration one day before cisplatin. Intratympanic dexamethasone injection 1h before cisplatin treatment resulted in a significant preservation of the functional and structural properties of the cochlea. Intratympanic dexamethasone administration is a safe, easy and efficient way to protect from cisplatin ototoxicity especially when administered 1h before cisplatin treatment.

Intratympanic Dexamethasone to Prevent Cisplatin Ototoxicity

To determine whether intratympanic administration of dexamethasone reduces ototoxicity from systemic cisplatin. Prospective animal study. Setting. Cisplatin chemotherapy induces ototoxicity manifesting as irreversible, sensorineural hearing loss. This is due to damage to the inner ear structures by free radicals. Steroidal anti-inflammatories have been shown to reduce the formation of free radicals and protect hearing in animal models. Pure tone auditory brainstem responses were obtained in 58 female albino guinea pigs before and 3 days after intraperitoneal (IP) cisplatin chemotherapy. Auditory brainstem responses were also taken up to 1 month after a low dose of cisplatin. Part I consisted of a dosing study to determine the optimal ototoxic dose of cisplatin. In part II, auditory brainstem response thresholds were compared after bilateral intratympanic dexamethasone doses to act as controls. For part III, the otoprotection of dexamethasone against cisplatin was tested in separate bilateral and unilateral studies. IP injection of 12 mg/kg of cisplatin induced significant hearing loss (57.2 ± 4.4 dB, P < .01) with 0% mortality. Ears treated with intratympanic dexamethasone alone showed no significant threshold changes. Ears that received IP cisplatin and intratympanic dexamethasone showed reduced threshold shifts at 8 kHz when the greatest concentration of dexamethasone was administered. Modest intratympanic dexamethasone otoprotection of the guinea pig ear was greatest at the highest concentration tested and occurred in a frequency-dependent manner. Intratympanic dexamethasone presents as a safe, simple, and effective treatment modality to minimize cisplatin ototoxicity without interfering with the chemotherapeutic effects of cisplatin.

Daily Short-Term Intratympanic Dexamethasone Treatment Alone as an Initial or Salvage Treatment for Idiopathic Sudden Sensorineural Hearing Loss

Objective: Intratympanic (IT) steroid therapy has been proposed as an alternative treatment option for patients with idiopathic sudden sensorineural hearing loss (ISSNHL). However, the number and frequency of IT treatments and drug delivery methods remain to be determined. The purpose of this study was to evaluate the efficacy of daily short-term IT dexamethasone (DEX) treatment alone in ISSNHL patients using laser-assisted myringotomy (LAM) for the drug delivery route as an initial and/or salvage treatment. Study Design: Retrospective study. Setting: University hospital. Patients: Seventy-six ISSNHL patients receiving IT DEX. Patients with low-tone hearing loss, unilateral or bilateral fluctuating hearing loss or contralateral hearing loss were excluded. Intervention: DEX (4 mg/ml) was injected through a perforation made by LAM. IT DEX administration was performed on 8 sequential days. Main Outcome Measures: Pre- and postprocedure hearing levels. The average hearing level was determined by 5 frequencies (250, 500, 1000, 2000 and 4000 Hz). Results: Nineteen out of 76 patients fit the criteria for initial treatment in the study (group I), while 24 patients, who had failed systemic therapy, received salvage treatment (group S). The mean age of the patients in groups I and S was 56.2 years with a range from 31 to 73 years of age and 46.0 years with a range from 11 to 76 years of age, respectively. The mean number of days from onset of symptoms to IT therapy in groups I and S was 4.8 days with a range of 1–23 days and 15.3 days with a range of 6–28 days, respectively. In group I, 18 of the 19 patients (95%) showed improvement of more than 10 dB in the pure-tone audiogram, with a mean improvement of 40 dB. Twelve patients (63%) recovered completely and 16 patients (84%) demonstrated successful results with an improvement of more than 30 dB. In group S, 14 of the 24 patients (58%) showed improvement of more than 10 dB with a mean improvement of 16 dB. Two (8%) of the 7 patients (29%) with successful results recovered completely. Conclusions: Daily short-term IT DEX administration using LAM for ISSNHL patients without concurrent therapy showed a high response rate and high cure rate and proved to be an alternative therapeutic option to high-dose systemic steroids as a first- and/or second-line treatment.

The Role of Fibrinolysis in Adhesive Otitis Media(AOM)

ObjectiveTo study the effects of Batroxobin on otitis media with effusion (OME), an early stage of Adhesive Otitis Media (AOM), for the purpose of expanding our understanding of the role of fibrinolysis in the pathogenesis of AOM. MethodForty cases of OME (45 ears) were randomly selected to receive intratympanic administration of Dexamethasone at 5 mg/ml (Group 1 or G1), Batroxobin at 1 BU/ml (Group 2 or G2) or Batroxobin at 2 BU/ml (Group 3 or G3). Pre– and post–treatment changes in clinical symptoms, the Air conduction Hearing Threshold (AHT) in pure tone audiometry and average AHT over 0.25 to 2kHz were compared. ResultsData from 31 cases (33 ears) were available for analysis. AHTs among three groups were similar prior to treatment (P> 0.05). The rate of normal hearing following treatment in G3 was 70% or 7/10, higher than in G1 (41.7% or 5/12) and G2(54.5% or 6/11) (P < 0.05). The rate of improvement following treatment was 81.8% or 9/11 and 80.0% or 8/10 in G2 and G3, respectively, higher than that in G1 (50.0% or 6/12) (P < 0.05). ConclusionsTherapeutic effects of intratympanic injection of Batroxobin on OME is superior to traditionally used Dexamethasone. In addition, higher concentration of Batroxobin appears to be superior to lower concentrations. These findings confirm that fibrinolysis plays a pivotal role in the pathogenesis of middle ear adhesion and that fibrinolytic medicine can prevent or reduce adhesion development in the middle ear.

Cisplatin-Induced Ototoxicity

Intratympanic (IT) application of dexamethasone will reduce ototoxicity associated with systemic cisplatin therapy. Cisplatin is a common chemotherapeutic drug often dose-limited by ototoxicity attributed to the formation of reactive oxygen and nitrogen species damaging critical inner ear structures. Steroids have been shown to reduce formation of reactive oxygen species and thus may reduce ototoxicity. In the present pilot study, we test this hypothesis by IT administration of dexamethasone in a novel murine model of cisplatin ototoxicity. Click- and pure-tone-evoked auditory brainstem responses (ABRs) in young CBA/J mice were measured. The first phase consisted of a dosing study to identify the optimal cisplatin dose for ototoxicity. In the next phase, ABR thresholds were measured in cisplatin-treated mice after 5 days of IT injection of 24 mg/ml of dexamethasone in 1 ear and normal saline in the opposite ear to serve as controls. Intraperitoneal injection of 14 mg/kg of cisplatin induces significant hearing loss (click-evoked ABR threshold elevation = 12 +/- 7 dB, mu +/- standard error of the mean) with acceptable mortality (20%). The ears that received IT dexamethasone in cisplatin-treated mice had minimal ABR threshold shifts with the click, 8 and 16 kHz of stimuli. There was no significant difference between IT dexamethasone and IT saline ears at 32 kHz. IT dexamethasone protected the mouse ear against cisplatin-induced ototoxicity in a frequency-dependent manner. The present results suggest that IT dexamethasone may be a safe, simple, and effective intervention that minimizes cisplatin ototoxicity without interfering with the chemotherapeutic actions of cisplatin.

Comparison of Intratympanic and Intravenous Dexamethasone Treatment on Sudden Sensorineural Hearing Loss with Diabetes

The purpose of this study was to evaluate the efficacy of intratympanic administration of dexamethasone (IT-DEX) treatment on sudden sensorineural hearing loss (SSNHL) patients with diabetes by comparing the results with intravenous administration of dexamethasone (IV-DEX) treatment. Comparative study. University hospital and affiliated hospital. Ten sequential SSNHL patients with diabetes receiving IT-DEX and 21 sequential SSNHL patients with diabetes receiving IV-DEX. Patients with low tone hearing loss were excluded. In the IT-DEX group, two methods were applied to deliver DEX (4 mg/ml): injection through a perforation made by laser-assisted myringotomy or through a tympanostomy tube. IT-DEX administration was performed on 8 sequential days. In the IV-DEX group, DEX was administrated intravenously starting from an amount of 8 mg/d followed by taped doses for 10 days. Preprocedure and postprocedure hearing levels and complications. In the IT-DEX group, the average hearing level before the treatment was 79 dB. Overall, all 10 patients showed improvement of more than 10 dB in the pure-tone audiogram, with a mean improvement of 41 dB. Seven patients (70%) demonstrated successful results, and four recovered completely. In the IV-DEX group, 14 (67%) of the 21 patients showed improvement of more than 10 dB with a mean improvement of 25 dB. Thirteen patients (62%) demonstrated successful results. Free blood sugar during and after the IT-DEX treatment remained below the pretreatment levels, whereas four patients in the IV-DEX group demonstrated worsening of the hyperglycemia. IT-DEX treatment is at least as effective as IV-DEX treatment for SSNHL patients with diabetes.

A comparative study of intratympanic steroid and NO synthase inhibitor for treatment of cochlear lateral wall damage due to acute otitis media

We studied the damage to the cochlear lateral wall induced by otitis media and the therapeutic effects of intratympanic administration of steroid and nitric oxide (NO) synthase inhibitor. In Sprague–Dawley rats, right middle ear cavities were inoculated with lipopolysaccharide, followed after 30 min by intratympanic administration of dexamethasone, NOS-inhibitor or PBS. Twenty-four hours after lipopolysaccharide inoculation, cochlear blood flow was measured by laser-Doppler flowmetry. Prostaglandin E 1 was topically applied to the round window membrane of the right ear and changes in cochlear blood flow were calculated. Changes of cochlear blood flow were significantly different among the three groups. Increases in cochlear blood flow following PGE 1 application were higher in the group that received NOS-inhibitor. Electron microscopic examination revealed that changes in the stria vascularis were less severe in rats treated with dexamethasone or NOS-inhibitor. Our results show the effectiveness of intratympanic dexamethasone or NOS-inhibitor in treating cochlear lateral wall damage caused by otitis media.